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We investigated the effects of water-soluble low-molecular-weight β-(1,3-1,6) D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast (LMW-β-glucan) on mast cell-mediated anaphylactic reactions. Although it is known that LMW-β-glucan has anti-tumor, anti-metastatic and anti-stress effects, the roles of LMW-β-glucan in immediate-type allergic reactions have not been fully investigated. We examined whether LMW-β-glucan could inhibit mast cell degranulation and passive cutaneous anaphylaxis (PCA). LMW-β-glucan dose-dependently inhibited the degranulation of both rat basophilic leukemia (RBL-2H3) and cultured mast cells (CMCs) activated by calcium ionophore A23187 or IgE. However, LMW-β-glucan had no cytotoxicity towards RBL-2H3 cells and CMCs. Furthermore, orally administered LMW-β-glucan inhibited the IgE-induced PCA reaction in mice. These results show LMW-β-glucan to be a possible compound for the effective therapeutic treatment of allergic diseases.

β-glucan, mast cell degranulation, passive cutaneous anaphylaxis, anti-allergic effect

NCBI PubMed ID: 22232243
Publication DOI: 10.1271/bbb.110536
Journal NLM ID: 9205717
Publisher: Japan Society for Bioscience, Biotechnology, and Agrochemistry
Correspondence: k-jippou@cs.kinran.ac.jp
Institutions: Department of Food and Nutrition, Faculty of Human Life Sciences, Senri Kinran University, Suita, Japan, Research and Development Department, Daiso Co., Ltd., Amagasaki, Japan
Methods: biological assays, extraction, gel chromatography, cell growth, precipitation, centrifugation, MTT

Though it has been reported that β-glucans or protein-binding hetero-glucans isolated from mushrooms have antitumor activity, the antitumor and antimetastatic actions of purified, structurally defined polysaccharides (such as β-glucans) have not been proven yet. A new low molecular weight (approximately 100 kDa) β-glucan was isolated from Aureobasidium pullulans black yeast, and was found to have low viscosity and to be water-soluble. The industrial production of this P-glucan was achieved from the culture media of A. pullulans. The effects of water-soluble low-molecular-weight (LMW) β-(1→3) and 50-80% branched β-(1→6) glucan isolated from A. pullulans on tumor growth and metastasis to the liver were examined in mice intrasplenically with implanted colon 26 tumor cells. In addition, to clarify the antitumor and antimetastatic actions of LMW β-(1,3-1,6) glucan, the effects on immune functions in the small intestine were also examined. The intraperitoneal (5 and 15 mg/kg) and oral (50 mg/kg) administration of LMW P-(1.3-1.6) glucan inhibited the tumor growth and liver metastasis in mice intrasplenically implanted with colon 26 cells. The numbers of natural killer (NK)- and interferon (IFN)-gamma-positive cells in the small intestine of colon 26-bearing mice were lower than those in normal mice. The intraperitoneally and orally administered LMW β-(1,3-1,6) glucan prevented the reduction of the number of NK- and IFN-gamma-positive cells induced by the tumor growth after implantation of colon 26 cells. These findings suggest that the antitumor and antimetastatic actions of LMW β-(1,3-1,6) glucan may involve the enhancement of intestinal immune functions through increases in NK- and IFN-gamma-positive cell numbers.

antitumor, water-soluble low-molecular-weight β-(1→3) with β-(1→6) D-glucan, antimetastasis, small intestinal immune function

NCBI PubMed ID: 17201124
Journal NLM ID: 8102988
Publisher: Attiki, Greece: International Institute of Anticancer Research
Correspondence: Kimura Y
Institutions: Division of Biochemical Pharmacology, Department of Basic Medical Research, Graduate School of Medicine, Ehime University, Toon, Japan, Division of Functional Histology, Department of Functinal Biomedicine, Graduate School of Medicine, Ehime University, Toon, Japan, Research and Development, Daiso Co. Ltd., Amagasaki, Japan
Methods: 13C NMR, 1H NMR, NMR-2D, biological assays, extraction, gel chromatography, cell growth, cytotoxicity assay, precipitation, antitumor activity assay, centrifugation, interleukin-6 assay

There have been a number of reports showing that the crude β-glucan fraction prepared from various kinds of Basidiomycetes mushrooms acts as anti-cancer and anti-allergic reagent through stimulation of IFN-γ production. It has been reported, however, that the exposure of the airway to β-(1,3) d-glucan, contained in house dust, indoor moulds and some bacteria, potentiates the airway allergic response. It seems likely that the discrepant effects on immune function may be related to such factors as differences of the administration route, average molecular weight and water solubility. We isolated a new low-molecular-weight (about 100 kDa) β-glucan from Aureobasidium pullulans 1A1 strain of black yeast, and found that it had low viscosity and was water-soluble. In this study, we examined the effects of water-soluble low-molecular-weight β-(1→3) and 50–80% branched β-(1→6) glucan (LMW-β-Glucan) isolated from A. pullulans on the ova-albumin (OVA)-treated allergic reaction in mice. Feeding standard laboratory diets containing 0.5 and 1% LMW-β-Glucan significantly inhibited the OVA-specific IgE elevation compared to that in OVA-sensitized mice fed standard laboratory diet alone (control). Furthermore, feeding standard laboratory diets containing 0.5 and 1% LMW-β-Glucan inhibited the reduction of IL-12 and IFN-γ production from splenocytes and the reduction of CD8- and IFN-γ-positive cell number in the small intestine of the OVA-sensitized mice. These findings suggest that anti-food allergic action of LMW-β-Glucan may be due to the inducing IFN-γ production in the small intestine and splenocytes.

food allergy, Ova-albumin, water-soluble low-molecular-weight β-(1, 3–1, 6) D-glucan, Th1/Th2

NCBI PubMed ID: 17499199
Publication DOI: 10.1016/j.intimp.2007.03.003
Journal NLM ID: 100965259
Publisher: Amsterdam; New York: Elsevier Science
Correspondence: Kimura Y
Institutions: Division of Biochemical Pharmacology, Department of Basic Medical Research, Graduate School of Medicine, Ehime University, Toon, Japan, Division of Functional Histology, Department of Functinal Biomedicine, Graduate School of Medicine, Ehime University, Toon, Japan, Research and Development, Daiso Co. Ltd., Amagasaki, Japan
Methods: 13C NMR, 1H NMR, TLC, biological assays, enzymatic digestion, extraction, gel chromatography, cell growth, cytokine production, precipitation, centrifugation

It is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. It has been reported that glucocorticoids suppress natural killer (NK) activity and interleukin (IL)-1 production and, on the other hand, that IL-1 and IL-6 stimulate the release of corticotrophin-releasing-hormone from the rat hypothalamus. Moreover, it has been reported that IL-12 plays a central role in the initiation of cell-mediated immunity, directly and via its induction of interferon (IFN)-gamma and activation of NK cells. In this study, we examined the effects of water-soluble low-molecular-weight β-glucan isolated from Aureobasidium pullulans 1A1 strain on the corticosterone levels and immune function, such as NK activity and IL-6 and IL-12 production, using a restraint stress-induced mouse model. The water-soluble low-molecular-weight β-glucan at a dose of 50 or 100 mg/kg inhibited the increases in the blood corticosterone level and the reduction of NK activity induced by restraint stress. Furthermore, the water-soluble low-molecular-weight β-glucan (100 mg/kg) prevented the reduction of IL-6 and IL-12 production by splenocytes caused by restraint stress. These findings suggest that the inhibitory actions of water-soluble low-molecular-weight β-glucan on the increase in corticosterone level and reduction of NK activity induced by restraint stress may be associated with the abrogation of the IL-6 and IL-12 reduction caused by the stress. Thus, water-soluble low-molecular weight β-glucan may be an effective dietary supplement for the prevention of stress.

stress, water-soluble low-molecular-weight β-(1, 3–1, 6) D-glucan, splenocytes production, cell-mediated immunity

NCBI PubMed ID: 17725857
Publication DOI: 10.1211/jpp.59.8.0012
Journal NLM ID: 0376363
Publisher: London: Pharmaceutical Society of Great Britain; West Sussex: Wiley
Correspondence: Kimura Y
Institutions: Division of Biochemical Pharmacology, Department of Basic Medical Research, Graduate School of Medicine, Ehime University, Toon, Japan, Division of Functional Histology, Department of Functinal Biomedicine, Graduate School of Medicine, Ehime University, Toon, Japan, Research and Development, Daiso Co. Ltd., Amagasaki, Japan
Methods: 13C NMR, 1H NMR, TLC, biological assays, enzymatic digestion, extraction, gel chromatography, cell growth, cytokine production, precipitation, centrifugation